BRCA1 is associated with a human SWI/SNF-related complex: Linking chromatin remodeling to breast cancer

Germline mutations in the tumor suppressor gene, BRCA1, predispose individu als to breast and ovarian cancers. Using a combination of affinity- and con ventional chromatographic techniques, we have isolated a predominant form o f a multiprotein BRCA1-containing complex from human cells displaying chrom atin-remodeling activity. Mass spectrometric sequencing of components of th is complex indicated that BRCA1 is associated with a SWI/SNF-related comple x. We show that BRCA1 can directly interact with the BRG1 subunit of the SW I/SNF complex. Moreover, p53-mediated stimulation of transcription by BRCA1 was completely abrogated by either a dominant-negative mutant of BRG1 or t he cancer-causing deletion in exon 11 of BRCA1. These findings reveal a dir ect function for BRCA1 in transcriptional control through modulation of chr omatin structure.